Impact of Biomarkers on Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants

Cui Yimin1,200 enrolled

Overview

It is general that there are many factors for individual differences of drugs in clinical application, of which genetic factors accounted for more than 20%. Novel oral anticoagulants-NOACs (include rivaroxaban, apixaban, dabigatran and so on) have advantages of convenient use and no need of monitoring, compared with the traditional vitamin K antagonist. With lack of predicted biomarkers, especially the research data of Chinese, it has the important significance in studying individual differences of NOACs in the anticoagulant efficacy and safety, through the pharmacogenomics research. The aim of this study is to determine the polymorphism of drug metabolizing enzymes, drug transporters and drug target genes in Chinese population. By detecting the gene polymorphism, we intend to study the pharmacokinetic/ pharmacodynamics/ pharmacogenomics (PK-PD-PG) correlation of NOACs and provide scientific basis for accurate medication guide for people to use NOACs.

Study Type

OBSERVATIONAL

Enrollment

1,200

Conditions

Novel Oral Anticoagulants NOACs Rivaroxaban Apixaban Dabigatran Pharmacokinetics

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: (I)Chinese Healthy Volunteers * In accordance with the inclusion criteria for each bioequivalence trial of NOACs; * Sign informed consent of the research; * Complete to collect indexes of pharmacodynamics and pharmacogenomics in the cycle with control drug. (II)Chinese Patients * In accordance with anticoagulation indications of NOACs, include prevention of thrombosis in non valvular atrial fibrillation, prevention and treatment of deep vein thrombosis / pulmonary embolism and prevention of thrombosis after knee / hip replacement; * More than 18 years of age, male or female; * Never received NOACs in a month and intend to take NOACs or have received NOACs for more than one week continuously; * sign informed consent. Exclusion Criteria: (I)Chinese Healthy Volunteers * In accordance with the exclusion criteria for each bioequivalence trial of NOACs; (II)Chinese Patients * With history of immunodeficiency disease, including positive HIV index; * Positive Hepatitis B surface antigen (HBsAg) and HCV index; * Combined therapy of CYP3A4 strong inhibitors and P-gp inhibitors (e.g., systemic pyrrole antifungal agents such as ketoconazole, itraconazole, voriconazole and posaconazole; human immunodeficiency virus (HIV) - protease inhibitors such as ritonavir), CYP3A4 strong inducers and P-gp inducers (e.g., rifampicin, phenytoin, phenobarbital, carbamazepine, St. John's Wort, etc.) in 14 days before treatment with NOACs; * Severe liver dysfunction and abnormal renal function; * Include contraindications of NOACs, such as hypersensitivity, active bleeding, moderate or severe liver disease, previous history of intracranial hemorrhage, gastrointestinal hemorrhage in the past 6 months and major operation within 30 days.

Locations (17)

Anhui Provincial Hospital（The First Affiliated Hospital Of USTC）

Hefei, Anhui, China

RECRUITING

Peking University First Hospital

Beijing, Beijing Municipality, China

RECRUITING

Beijing Hospital

Beijing, Beijing Municipality, China

RECRUITING

Beijing HuiLongGuan Hospital

Beijing, Beijing Municipality, China

ACTIVE_NOT_RECRUITING

The Second Affiliated Hospital Of Chongqing Medical University

Chongqing, Chongqing Municipality, China

RECRUITING

Fujian Medical University Union Hospital

Fuzhou, Fujian, China

ACTIVE_NOT_RECRUITING

900 Hospital of the Joint Logistics Team (Original name: Fuzhou General Hospital of Nanjing Militray Command)

Fuzhou, Fujian, China

RECRUITING

The 7th People's Hospital of Zhengzhou

Zhengzhou, Henan, China

RECRUITING

The Third Hospital of Changsha

Changsha, Hunan, China

ACTIVE_NOT_RECRUITING

Wuxi People's Hospital

Wuxi, Jiangsu, China

WITHDRAWN

...and 7 more locations

Outcomes

Primary Outcomes

Incidence of stroke or systemic embolic events (including TIA)

During the observation time, record the incidence of stroke or systemic embolic events (including TIA) after NOACs(rivaroxaban, apixaban, dabigatran) administration by telephone or out-patient clinic.

Time frame: At 1 year

Incidence of bleeding events

During the observation time, record the incidence of bleeding events after NOACs(rivaroxaban, apixaban, dabigatran) administration by telephone and out-patient clinic, including subcutaneous bleeding, gingival bleeding, gastrointestinal bleeding, intracranial hemorrhage, etc.

Time frame: At 1 year

Secondary Outcomes

Genotype detected by next generation sequencing

Collect blood specimen before NOACs administration, then detect genotype of NOACs by next generation sequencing.

Time frame: pre-dose of NOACs (rivaroxaban, apixaban, dabigatran)

Level of anticoagulant activity assessed by anti-factor Xa activity

Before and after rivaroxaban and apixaban administration, record anti-factor Xa activity detected by blood coagulation tests.

Time frame: At baseline; at 3 hours, at 8 or 9 hours, at 12 hours for Chinese healthy volunteers, at 48 or 72 hours for Chinese patients

Level of anticoagulant activity assessed by anti-factor IIa activity

Before and after dabigatran administration, record anti-factor IIa activity detected by blood coagulation tests.

Time frame: At baseline; at 2 hours, at 4 hours, at 8 hours, at 12 hours for Chinese healthy volunteers, at 72 hours for Chinese patients

Expression level of miRNA

Before and after NOACs administration, detect the expression level of miRNA about pharmacodynamics.

Time frame: At baseline; at 2 or 3 hours, at 4 hours (only for dabigatran), at 8 or 9 hours, at 12 hours for Chinese healthy volunteers, at 48 or 72 hours for Chinese patients.

Expression level of LncRNA

Before and after NOACs administration, detect the expression level of LncRNA about pharmacodynamics.

Time frame: At baseline; at 2 or 3 hours, at 4 hours (only for dabigatran), at 8 or 9 hours, at 12 hours for Chinese healthy volunteers, at 48 or 72 hours for Chinese patients.

Incidence of stroke or systemic embolic events in the other observation times

During the other observation time, record the incidence of stroke or systemic embolic events (including TIA) after NOACs(rivaroxaban, apixaban, dabigatran) administration by telephone or out-patient clinic.

Time frame: At 1 month, 6 months and 2 years (according the actual duration of NOACs taken in patiens)

Incidence of bleeding events in the other observation times

During the other observation time, record the incidence of bleeding events after NOACs(rivaroxaban, apixaban, dabigatran) administration by telephone and out-patient clinic, including subcutaneous bleeding, gingival bleeding, gastrointestinal bleeding, intracranial hemorrhage, etc.

Time frame: At 1 month, 6 months and 2 years (according the actual duration of NOACs taken in patiens)

Impact of Biomarkers on Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants

Overview

Conditions

Interventions

Eligibility

Locations (17)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts